Objective　To explore the mechanism of male reproductive toxicity of bisphenol-A.Methods　The morphological characteristics of seminiferous tubule,vimentin filaments and p53 gene expression in sertoli's cells of adult SD rats orally exposed to 0.5% bisphenol-A were observed and analyzed by histo-chemical and immuno-histochemical methods.Results　After 2-week-exposure to 0.50% bisphenol-A,the disattachment between sertoli's cell and spermatogonia,spermatogonia arranged in disorder and displacement of spermatogonia away from the basement membrance of seminiferous tubules as well as the flocculated chromatins of nuclei in sertoli's cells and spermatogonia were observed.Fourfold increase of p53 expression in nuclei of spermatogonia and leydig's cells and the collaps of vimentin filaments in sertoli's cells were also found.Conclusion　The results suggested that the disattachment between sertoli's cells and spermatogonia,might be associated with the collaps of vimentin filaments in nuclei of sertoli's cells and the increase of p53 expres sion in nuclei of sertoli's cells and spermatogonia,which might be one of the important mechanisms of reproductive toxicity of bisphenol-A.The increase of p53 expression in nuclei of leydig's cells might predict the potential anti-androgenicity of bisphenol-A

Objective To establish a method to investigate micronuclei (MN) and gene mutation at the heterozygous thymidine kinase (tk) locus induced by environmental mutagens in TK6 human lymphoblastiod cells. Methods TK6 cells were used to detect cytotoxic response, MN and mutation frequency at tk locus induced by cyclophosphomide (CP) after treatment with S9 mixture for 4 h. Results Exposure to CP for 4 h decreased relative survival (RS), induced both MN and TK mutation in a concetration-dependent manner. The maximum induction of MN and TK mutations were 8.8 and 15.7 times compared with those of control. Two distinct phenotypic colonies of TK mutants were generated, namely tk-NG and tk-SG mutant colonies but mainly the latter. Conclusion CP induced both MN and TK mutation in TK6 cells. TK6 cells can be used as an in vitro assay system to assess cytogenetic damage and gene mutation at tk locus of environmental chemicals.

Objective To understand the clinical feature of the elderly patients with diabetes during coronary angiography,and analyze the risk factors of contrast-induced nephropathy (CIN).Methods The clinical data of 269 elderly patients who had undergone coronary angiography and percutaneous coronary intervention(PCI) from January 2007 to December 2009 in our hospital were analyzed retrospectively.The patients were divided into two groups:CIN group and non-CIN group.The possible risk factors for CIN,such as glycemic control,diabetic complication,renal function,volume of contrast medium,inflammatory state,therapy of perioperative period,past medical history were analyzed and compared between the two groups. Results In 269 elderly patients with diabetes,the incidence of CIN was 9.3 ％ (25/269).According to estimated glomerular filtration rate (e-GFR),the patients were divided into four subgroup:≥90 ml/min,89-60 ml/min,59-30 ml/min,＜29 ml/min.The incidences of CIN for the subgroups were 2.2％(1/45),4.4％(6/135),17.3％(14/81) and 50 ％ (4/8),respectively.Multivariate logistic gradual regressive analysis showed that loop diuretic use (OR＞ 6.07),preoperative e-GFR(＜60 ml/min) (OR＞3.27),volume of contrast medium (≥200ml) (OR＞3.26),chronic kidney disease(CKD) (OR＞2.80) (P=0.001,0.024,0.015,0.048) were indepen-dent risk factors for CIN (P＜0.05). Conclusions Loop diuretic use,preoperative GFR (＜60 ml/min),volume of contrast medium (≥200 ml) and CKD are independent risk factors of CIN.

Dendritic cells (DCs) as a rare type of leukocytes play an important role in bridging the innate and adaptive immune system. A subset of DCs, monocyte-derived dendritic cells (moDCs), exists in very low numbers at steady state but become abundant in inflammatory states. These inflammation-associated DCs are potent producers of pro-inflammatory cytokines and potent inducers of T helper differentiation. They behave as a "double-edge" sword so that they not only mediate protective immunity but also immuno-pathology. It is still incompletely understood how their function is regulated. Emerging evidence indicates that microRNAs (miRNAs), as a new class of gene regulators, potently regulate the function of moDCs. Here we summarize recent progress in this area.
Animals ; Antigen Presentation ; genetics ; Cell Differentiation ; Cytokines ; genetics ; metabolism ; Dendritic Cells ; metabolism ; physiology ; Humans ; Inflammation ; immunology ; pathology ; MicroRNAs ; metabolism ; physiology ; RNA Interference

Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Oncogene Proteins, Viral ; genetics ; Papillomavirus E7 Proteins ; Plasmids ; RNA, Messenger ; metabolism ; Repressor Proteins ; genetics ; Transfection ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

Objective To investigate the effect of dexamethasone combined with oridonin on proliferation and apoptosis in multiple myeloma cells U266 and the related molecular mechanism. Methods Exponential phase of growth U266 cells were treated with different concentrations of oridonin combined with dexamethasone or alone. U266 cells treated by DMSO were taken as control group. The proliferation inhibitory ratios were measured by CCK-8 assay followed by 24 h, 48 h and 72 h. Apoptosis induction was assessed by using Annexin V-FITC kit. Real time PCR was used to examine the mRNA changes of Notch1, NF-κB/p65 and bcl-2. Western blot assay was applied to detect the protein expression of Notch1, cleaved Notch1, NF-κB/p65 and bcl-2. Results Compared with that in control group, proliferation in all the experimental groups was inhibited (P<0.05), and the apoptosis was promoted (P<0.05); especially the combination of dexamethasone and oridonin had a synergistic effect on the proliferation and apoptosis of U266 cells (P<0.05). The results of PCR and Western blot showed that after treatment of U266 cells with dexamethasone, the mRNA as well as their protein levels of NF-κB/p65 and bcl-2 were decreased compared with those in the control group (P<0.05). Moreover, the mRNA and protein expression of Notch1, cleaved Notch1, NF-κB/p65 and bcl-2 was obviously down-regulated in oridonin group and the combination group (P<0.05). Conclusion Combination of dexamethasone and oridonin can significantly increase the anti-tumor effect by inhibiting proliferation and inducing apoptosis of U266 cells, which may be related to the inhibition of the Notch1 pathway.

OBJECTIVE: To observe the therapeutic effect of Xincang Decoction on chronic airway inflammation in children with asthma in clinical investigation. METHODS: Xincang Decoction was composed of Flos Magnoliae (Xinyi) and Fructus Xanthii (Cangoerzi), the traditional Chinese herbs for expelling wind. Sixty cases of children with bronchial asthma in remission stage were randomly divided into two groups. Thirty cases in the treatment group were treated with Xincang Decoction and the others in the control group were treated with ketotifen fumarate. The therapeutic effects of the two groups were compared, and the peripheral eosinophil (EOS) count, the levels of immunoglobulin E (IgE), interleukin 4 (IL-4) and interleukin 5 (IL-5), and the pulmonary functions were observed before and three months after the treatment. RESULTS: After three months treatment, the results showed that the total response rates of the treatment and the control group were 83.3% and 80.0%, respectively, without marked difference (P>0.05). The levels of EOS and IL-5 were obviously decreased after the treatment, and the levels of EOS and IL-5 of the patients in the treatment group were lower than those in the control group (P<0.05). Meanwhile the forced expiratory volume in one second (FEV(1)) was improved after the treatment, and the FEV(1) of the patients in the treatment group was higher than that of the patients in the control group (P<0.05). CONCLUSION: Xincang Decoction can decrease the levels of EOS and IL-5 and improve the pulmonary function in treating chronic airway inflammation in children with bronchial asthma in remission stage.

Objective To observe the changes of zymophagy during experimental acute pancreatitis (AP) induced by caerulein.Methods Pancreatic acinar cell line AR42J cells were cultured in 6-well plates till 90％ confluent and then divided into AP group and control group.Caerulein (1 × 10-8 mol/L) was added into AP group to establish AP cell model,and 1640 cell culture medium was added into control group.After caerulein treated for one,four,six,eight,12 and 24 hours,cells and cell culture supernatant were collected.The levels of cytokine interleukin (IL)-1,tumor necrosis factor (TNF)α,trypsinogen activation (TAP) and amylase were measured with enzyme-linked immunosorbent assay (ELISA) method.The expression of LC3 and Beclin1 at mRNA of each group were detected by reverse transcription-polymerase chain reaction (RT-PCR).The LC3B protein level of each group were detected by Western blotting.The changes of autophagosome and zymophagosome were observed by transmission electron microscopy.The difference between AP group and control group was analyzed by analysis of variance.Results The level of IL-1,TNFα,amylase and TAP in cell culture supernatant of control group was (18.83±7.10) pg/mL,(14.20±3.79) pg/mL,(10.03±2.85) U/L and (39.48±8.62) pg/mL,respectively.Those of AP group significantly increased at first hour ((62.13±11.25) pg/mL,F=3.32,P＜0.01 ; (30.98±7.11) pg/mL,F=3.05,P＜0.05; (25.06±6.82) U/L,F=2.90,P＜0.05 and (128.51± 18.30) pg/mL),F=2.62,P＜0.01,at fourth or sixth hour reached peak (IL-1 at fourth hour:(71.96± 15.82) pg/mL,F=7.25,P＜0.01;TNFα at sixth hour:(39.92±8.94) pg/mL,F=4.93,P＜0.05; amylase at fourth hour:(28.83 ± 8.31) U/L,F=2.06,P＜0.05; TAP at fourth hour:(146.29± 29.36) pg/mL,F=0.14,P＜0.01) and then gradually decreased.At fourth and sixth hour,the expression of LC3 at mRNA level in AP group was 3.18±0.82,1.71±0.14,respectively,while the expression of Beclin-1 rnRNA at first,fourth hour was 2.44±0.34 and 4.13±0.30,all of them were significantly increased compared with those of control group (0.21±0.04 and 0.30±0.08,LC3 mRNA F=0.79、0.06; Beclin mRNA F=2.31、0.36,all P＜ 0.05).There were no significant differences at other time points.The numbers of autophagosome and zymophagosome of AP group were significantly higher than those of control group under transmission electron microscopy.Conclusion Zymophagy occurred during AP cell model induced by caerulein,which suggested that zymophagy might involve in the mechanism of AP.

Background:Damage of intestinal mucosal barrier is a key factor in the development and progress of acute pancreatitis(AP),and is closely related with the prognosis of the disease. Aims:To investigate the protective effect and possible mechanism of mucoprotective agent teprenone on intestinal mucosal barrier in rats with experimental AP. Methods:Forty-five adult male Sprague-Dawley rats were randomly divided into normal control group(n = 5),AP model group(n = 20)and teprenone treated group(n = 20). AP model was established by subcutaneous injection of cerulein at abdominal wall. Rats in treated group were intervened with teprenone intragastrically before and after model establishment. ELISA was used for measurement of serum interleukin-1(IL-1),IL-6,tumor necrosis factor-α(TNF-α)and amylase;histopathological and ultrastructural changes of small intestinal mucosa were observed by light microscope and transmission electron microscope;Western blotting was used to detect the expressions of tight junction protein occludin and ZO-1. Results:Serum levels of IL-1,IL-6,TNF-α and amylase in AP model group were significantly higher than those in normal control group(P < 0. 05),accompanied by necrosis and exfoliation of small intestinal villus,widening of intercellular tight junctions and downregulation of occludin and ZO-1 expression. While in teprenone treated group,serum levels of proinflammatory cytokines and amylase were significantly decreased as compared with AP model group(P < 0. 05),the villus of small intestine remained intact,and dense tight junctions were observed. Expressions of occludin and ZO-1 in teprenone treated group were upregulated. Conclusions:Teprenone may protect against intestinal mucosal barrier injury in AP model rats by upregulating tight junction protein expression.

Objective To investigate the effect of apatinib on the proliferation,apoptosis and migration of pancreatic cancer cell line AsPC-1 in vitro.Methods Pancreatic cancer AsPC-1 cells were treated by apatinib in different concentrations.Cell proliferation and apoptosis were measured by CCK-8 and flow cytometry,and the effect of apatinib on cell migration ability was observed by wound healing assay.Results In control and 10,20,30,40 and 50umol/L apatinib treatment group,the inhibitory rates of AsPC-1 cells were 0,(1.45 ±0.68)％,(16.92±0.70)％,(23.84±0.84)％,(34.35±1.55)％ and (37.33± 0.81) ％,respectively.Cell proliferation was obviously inhibited by apatinib as the concentration increased,and the differences were statistically significant (P ＜ 0.05).In control and 20,40 umol/L apatinib treatment group,the apoptotic rates were (9.44 ± 0.18) ％,(16.62 ± 0.19) ％ and (25.42 ± 0.41) ％,respectively.Number of apoptotic cells was obviously increased by apatinib as the concentration increased,and the differences were statistically significant (P ＜ 0.05).In control and 20,40 umol/L apatinib treatment group,the migration ability was (29.5 ± 0.7) ％,(17.4 ± 0.9) ％ and (6.6 ± 0.5) ％,which was greatly decreased as the concentration increased,and the differences were statistically significant (P ＜ 0.05).Conclusions Apatinib can effectively inhibit the proliferation and migration of pancreatic cancer AsPC-1 cells and induce apoptosis.